Lessons from the Long Haul in Diabetes

Joslin 50-Year Medalists, who often survive decades of diabetes with surprisingly few effects, begin to yield their secrets

This is an exceptional group—we’re still learning just how exceptional.

Many of the people who have been awarded a Joslin 50-Year Medal still are producing insulin, decades after being hit by the type 1 diabetes autoimmune attacks that destroy insulin-producing beta cells.

And in a detailed study of hundreds of Medalists published in April 2011, 43% of the group remained free of proliferative diabetic retinopathy, 39% were free from nerve damage, 52% free of cardiovascular disease and 87% free of kidney disease.

What gives—or rather, what doesn’t give way to diabetes in this select group of survivors?

“They are phenomenal,” says Hillary Keenan, Ph.D., co-principal investigator for the Joslin 50-Year Medalist study, which formally started in 2005 and is creating an ever-longer string of innovative research projects.

Beta cells that keep coming

A paper published in 2010 providing definitive proof that some Medalists still possess functioning beta cells, both growing and dying in the pancreas, was especially remarkable. “After 70 or 80 years, these cells are still constantly reproducing themselves, which is very exciting,” says George King, M.D., Joslin’s Chief Scientific Officer and principal investigator for the Medalist study.

Another groundbreaking project involving this exceptional group of patients is underway under the direction of Rohit Kulkarni, M.D., Ph.D., and Amy Wagers, Ph.D. The scientists are using skin cells from Medalists to create induced pluripotent stem (iPS) cells, which have the potential to differentiate into any type of cell in the body.

“With the iPS cells, we’ll generate insulin-secreting beta cells, and cells typically involved in complications that develop in patients with longstanding type 1 diabetes including vascular cells, kidney cells and eye cells,” says Dr. Kulkarni. These cells then can be analyzed for clues to their uncanny survival skills in Medalists.

The diabetic iPS cells “will model diabetes in a dish,” says Dr. Wagers. Previous Medalist research has identified a number of candidate molecular pathways to examine, she adds, and “the nice thing about having the iPS cells is that one can test out those individual pathways in the exact genetic background of the individual in which they’ve been identified. It gives us a much more controlled system to test the importance of genes that are associated with protection from diabetic complications.”

Finding safety factors

Other researchers in the Medalist study will examine more deeply how the cells that become involved in cardiovascular, eye and kidney disease may differ in that population.

Among these projects, Andrzej Krolewski, M.D., Ph.D., is leading an effort to compare all the protein-coding genes in two groups of people with diabetes: Medalists without serious eye or kidney complications, and others who developed serious complications within the first 25 years of diabetes. Genes that areproduced in greater numbers in the first group will be investigated further to identify factors that may protect against the complications.

Additionally, the study will compare the health histories of Medalists with those of other populations, including the parents of Medalists, another long-lived group. Yet another project will take a look at their psychological profiles—one of the most common attributes, apparently, is that Medalists like to dance!

Taken all together, the Medalist projects demonstrate Joslin’s unique strengths across the board in diabetes research. Only Joslin, declares Dr. King, can put together a study with this breadth and depth, with so many collaborations drawing on researchers with such a broad range of expertise, and with such promise for major impact on type 1 diabetes.

Volunteers for a groundbreaking program in diabetes research, a group of Joslin 50-Year Medalists gathered at the Center.